Abnormal growth rate in womb linked to autism

‘Babies that are abnormally heavy or underweight are at 62% greater risk’ of developing autism, reports the Daily Mail. The news is based on a large study of Swedish children with and without autism spectrum disorder (ASD).

Researchers compared healthy children up to the age of 17 with children who had a diagnosis of ASD. They examined whether there were any differences between the children in terms of how quickly they grew while in the womb (foetal growth) and the length of the pregnancy.

They found that babies with unusually low and unusually high levels of foetal growth had an increased risk of ASD (with or without intellectual disability).

This large study does suggest a possible association between foetal growth and ASD, but it does not prove a direct cause and effect. It could well be that there are underlying factors that cause both abnormal foetal growth and ASD.

While the researchers did try to account for a number of factors that could be linked to both foetal growth and ASD, this is not an exact science.

However, this study does raise interesting questions about how development in the womb could affect a child’s risk of ASD, and will hopefully lead to further research in this field.

Where did the story come from?

The study was carried out by researchers from Manchester and Bristol Universities, Karolinska University Hospital in Sweden, Columbia University in the US, and other institutions. Sources of funding were not reported. It was published in the peer-reviewed American Journal of Psychiatry.

The study was covered by the Daily Mail, whose reporting was arguably not as clear as it could have been. While the main findings of the study were reported accurately, there was no discussion about the limitations of the study, or that other factors could have been at play.

The headline and much of the reporting also focuses on birth weight. However, the researchers specifically did not want to use birth weight as the prime measurement, as they said this is often prone to inaccuracy and misinterpretation. This is why they took the decision to focus on foetal growth.

What kind of research was this?

This was a nested case-control study within the Stockholm Youth Cohort study looking at the associations between the growth of babies in the womb, gestational age (length of the pregnancy) and ASD.

Autism spectrumdisorder (ASD) is the name given to a group of developmental disorders that start in very early childhood and tend to have characteristic impairments in three main areas:

social interaction, such as having difficulty understanding emotions

communication and language difficulties

a restricted, repetitive collection of interests and activities, or set routines or rituals

ASD includes both autism and Asperger syndrome. The main difference between the two disorders is that children with autism tend to have some degree of learning difficulty or intellectual impairment, while this is less common in Asperger syndrome.

In some cases, children with Asperger syndrome can be particularly gifted in certain areas, such as mathematics or computer science, though this is less common than the media would lead you to believe.

The causes of ASD are not known. Current thinking on the matter speculates that a combination of genetic and environmental factors disrupts the development of the brain during pregnancy.

A nested case-control study is a special type of cohort study where people who have the condition (cases) and a selected matched group who don’t (controls) are selected from the same population, or cohort, of people (nested).

In contrast to non-nested case-control studies, data is usually collected prospectively, which means that researchers can be sure of when certain exposures or outcomes happened. This also avoids the difficulties or biases of participants remembering past events. Also, as cases and controls are selected from the same cohort, this means that they should be better matched than if researchers identified cases and controls separately.

What did the research involve?

The researchers used data from the Stockholm Youth Cohort study, which included all children up to the age of 17 who lived in Stockholm county between 2001 and 2007.

They identified 4,283 children with ASD (cases) and compared them with 36,588 healthy children randomly selected from the community (controls).

The cases were matched to controls by age and sex. For each child with ASD, there were nine children without the condition.

Of the children with ASD, 1,755 had an intellectual disability and 2,528 did not. Children who had been adopted or had missing data were excluded from the study.

Children with ASD were determined by linking with national registries containing information about all assessments or care of ASD in Stockholm county. The researchers say that children in Stockholm have assessments of development carried out by nurses or paediatricians at the ages of 1, 2, 6, 10-12, 18, 36, 48 and 60 months, or when there is concern about a child’s development.

They say the type of care a child receives following a diagnosis of ASD is determined by whether the child also has an intellectual disability or not. This allowed the researchers to determine how many children with ASD also had an intellectual disability.

The researchers then collected information on the birth weight of each child and the length of the pregnancy (gestational age). The length of the pregnancy was determined using ultrasound dating.

They used information from the national registry of births to determine averages of foetal growth by gestational age, so they could determine which children were above or below these averages.

The researchers analysed the results to determine the risk of developing ASD (with and without intellectual disability). Results were adjusted for known factors that may have influenced the results (confounders), including:

What were the basic results?

below-average foetal growth was associated with an increased risk of ASD – the poorer the growth, the higher the risk

foetal growth that was higher than average was associated with an increased risk of ASD, but only when the growth was in the extreme ranges of higher than normal

these findings were for children with and without intellectual disability, although below-average foetal growth was more strongly associated with ASD with intellectual disability than without

following adjustment, children who were born small or large for their gestational age were at greater risk of developing ASD with intellectual disability, irrespective of the length of the pregnancy

preterm birth increased the risk of ASD independent of foetal growth

The researchers also found:

parents of children with ASD were more likely to have experienced admission to hospital for psychiatric reasons (18.7%) compared with parents of children without ASD (11.3%)

children with ASD were more likely to have congenital malformations compared with children without ASD

How did the researchers interpret the results?

The authors concluded that foetal growth above or below the average in Stockholm is an independent risk factor for developing ASD. They say this risk is greatest when growth is well below or above average, as well as for ASD with intellectual disability.

The researchers suggest these findings may allow for the possibility of early intervention in order to reduce poor developmental outcomes, through monitoring as well as follow-up, screening and the management of children who may be most at risk.

Lead researcher Professor Kathryn Abel from Manchester University is reported as saying, “We think this increase in risk associated with extreme abnormal growth of the foetus shows that something is going wrong during development, possibly with the function of the placenta.”

Conclusion

This large study suggests a possible link between foetal growth and very low or very high birth weight and ASD, with or without intellectual disability. However, it only observes an association and does not prove cause and effect.

Parents expecting a baby who is showing below- or above-average foetal growth, or who have a baby born with below- or above-average birth weight, should not be overly concerned that their child may be at risk of developing ASD.

If there is a direct link between foetal growth and ASD, the reasons why this may be the case are not clear. The authors’ suggestions of possible reasons, such as the function of the placenta, are only theories.

Importantly, although the authors have tried to adjust for possible confounders, there could be other factors at play that may have affected the results. These include genetic, environmental or health-related conditions that the child or mother were exposed to during the pregnancy or after the birth.

Examples of possible factors not taken into consideration include alcohol and substance misuse, and obesity or weight gain around the time of the birth.

The study also only relates to a Swedish population sample. There may be environmental and population health differences between Sweden and elsewhere, meaning that care should be taken when generalising results to other countries.

Overall, the possible causes of autism spectrum disorder remain unknown, and further research is needed.